Bacterial translocation occurs early in cirrhosis and triggers a selective infammatory response

Background: Experimental data suggest that bacterial translocation (BT) promotes systemic inflammation, portal hypertension, and circulatory dysfunction in advanced chronic liver disease (ACLD). Methods: Patients with ACLD undergoing hepatic venous pressure gradient (HVPG) measurement and absence of...

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Autores: Simbrunner, Benedikt, Caparrós, Esther, Neuwirth, Teresa, Schwabl, Philipp, Königshofer, Philipp, Bauer, David, Marculescu, Rodrig, Trauner, Michael, Scheiner, Bernhard, Stary, Georg, Mandorfer, Mattias, Reiberger, Thomas, Francés, Rubén
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Universidad Miguel Hernández de Elche
Repositorio:REDIUMH. Depósito Digital de la UMH
OAI Identifier:oai:dspace.umh.es:11000/31334
Acceso en línea:https://hdl.handle.net/11000/31334
Access Level:acceso abierto
Palabra clave:Bacterial translocation
Circulatory dysfunction
Cirrhosis
Cytokine
Endotoxin
Gut–liver axis
Immunity
Inflammation
PAMPs
Portal hypertension
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spelling Bacterial translocation occurs early in cirrhosis and triggers a selective infammatory responseSimbrunner, BenediktCaparrós, EstherNeuwirth, TeresaSchwabl, PhilippKönigshofer, PhilippBauer, DavidMarculescu, RodrigTrauner, MichaelScheiner, BernhardStary, GeorgMandorfer, MattiasReiberger, ThomasFrancés, RubénBacterial translocationCirculatory dysfunctionCirrhosisCytokineEndotoxinGut–liver axisImmunityInflammationPAMPsPortal hypertensionBackground: Experimental data suggest that bacterial translocation (BT) promotes systemic inflammation, portal hypertension, and circulatory dysfunction in advanced chronic liver disease (ACLD). Methods: Patients with ACLD undergoing hepatic venous pressure gradient (HVPG) measurement and absence of acute decompensation or infections were included (n = 249). Serum biomarkers of BT (lipopolysaccharide [LPS], lipoteichoic acid [LTA], bacterial DNA [bactDNA]), systemic inflammation and markers of circulatory dysfunction were assessed. T-cell subsets in intestinal biopsies (n = 7 ACLD, n = 4 controls) were analyzed by flow cytometry. Results: Patients had a median HVPG of 18 (12-21) mmHg and 56% had decompensated ACLD. LPS (0.04 [0.02-0.06] vs. 0.64 [0.30-1.06] EU/mL), LTA (4.53 [3.58-5.97] vs. 43.2 [23.2-109] pg/mL), and detection of bactDNA (≥ 5 pg/mL; 5% vs. 41%) were markedly higher in patients with ACLD than healthy controls (n = 40; p < 0.001) but were similar between different clinical stages of compensated and decompensated ACLD and displayed no meaningful correlation with HVPG and systemic hemodynamics. TNF-α and IL-10 correlated with LPS (Spearman's rs = 0.523, p < 0.001/rs = 0.143, p = 0.024) but not with LTA. Presence of bactDNA was associated with higher LPS (0.54 [0.28-0.95] vs. 0.88 [0.32-1.31] EU/mL, p = 0.001) and TNF-α (15.3 [6.31-28.1] vs. 20.9 [13.8-32.9] pg/mL). Patients with ACLD exhibited a decreased CD4:CD8-ratio and increased TH1-cells in the intestinal mucosa as compared to controls. During a median FU of 14.7 (8.20-26.5) months, bacterial antigens did not predict decompensation or liver-related death (in contrast to HVPG, IL-6, and MAP) as well as infections at 24 months. Conclusion: BT occurs already in early ACLD stages and triggers a systemic inflammatory response via TNF-α and IL-10. Interestingly, BT markers showed no clear correlation with portal hypertension and circulatory dysfunction in patients with stable ACLD.SpringerDepartamentos de la UMH::Medicina Clínica202420242023info:eu-repo/semantics/articleapplication/pdf12application/pdfhttps://hdl.handle.net/11000/31334reponame:REDIUMH. Depósito Digital de la UMHinstname:Universidad Miguel Hernández de ElcheIngléshttps://doi.org/10.1007/s12072-023-10496-yinfo:eu-repo/semantics/openAccessAttribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/oai:dspace.umh.es:11000/313342026-05-27T13:36:21Z
dc.title.none.fl_str_mv Bacterial translocation occurs early in cirrhosis and triggers a selective infammatory response
title Bacterial translocation occurs early in cirrhosis and triggers a selective infammatory response
spellingShingle Bacterial translocation occurs early in cirrhosis and triggers a selective infammatory response
Simbrunner, Benedikt
Bacterial translocation
Circulatory dysfunction
Cirrhosis
Cytokine
Endotoxin
Gut–liver axis
Immunity
Inflammation
PAMPs
Portal hypertension
title_short Bacterial translocation occurs early in cirrhosis and triggers a selective infammatory response
title_full Bacterial translocation occurs early in cirrhosis and triggers a selective infammatory response
title_fullStr Bacterial translocation occurs early in cirrhosis and triggers a selective infammatory response
title_full_unstemmed Bacterial translocation occurs early in cirrhosis and triggers a selective infammatory response
title_sort Bacterial translocation occurs early in cirrhosis and triggers a selective infammatory response
dc.creator.none.fl_str_mv Simbrunner, Benedikt
Caparrós, Esther
Neuwirth, Teresa
Schwabl, Philipp
Königshofer, Philipp
Bauer, David
Marculescu, Rodrig
Trauner, Michael
Scheiner, Bernhard
Stary, Georg
Mandorfer, Mattias
Reiberger, Thomas
Francés, Rubén
author Simbrunner, Benedikt
author_facet Simbrunner, Benedikt
Caparrós, Esther
Neuwirth, Teresa
Schwabl, Philipp
Königshofer, Philipp
Bauer, David
Marculescu, Rodrig
Trauner, Michael
Scheiner, Bernhard
Stary, Georg
Mandorfer, Mattias
Reiberger, Thomas
Francés, Rubén
author_role author
author2 Caparrós, Esther
Neuwirth, Teresa
Schwabl, Philipp
Königshofer, Philipp
Bauer, David
Marculescu, Rodrig
Trauner, Michael
Scheiner, Bernhard
Stary, Georg
Mandorfer, Mattias
Reiberger, Thomas
Francés, Rubén
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Departamentos de la UMH::Medicina Clínica
dc.subject.none.fl_str_mv Bacterial translocation
Circulatory dysfunction
Cirrhosis
Cytokine
Endotoxin
Gut–liver axis
Immunity
Inflammation
PAMPs
Portal hypertension
topic Bacterial translocation
Circulatory dysfunction
Cirrhosis
Cytokine
Endotoxin
Gut–liver axis
Immunity
Inflammation
PAMPs
Portal hypertension
description Background: Experimental data suggest that bacterial translocation (BT) promotes systemic inflammation, portal hypertension, and circulatory dysfunction in advanced chronic liver disease (ACLD). Methods: Patients with ACLD undergoing hepatic venous pressure gradient (HVPG) measurement and absence of acute decompensation or infections were included (n = 249). Serum biomarkers of BT (lipopolysaccharide [LPS], lipoteichoic acid [LTA], bacterial DNA [bactDNA]), systemic inflammation and markers of circulatory dysfunction were assessed. T-cell subsets in intestinal biopsies (n = 7 ACLD, n = 4 controls) were analyzed by flow cytometry. Results: Patients had a median HVPG of 18 (12-21) mmHg and 56% had decompensated ACLD. LPS (0.04 [0.02-0.06] vs. 0.64 [0.30-1.06] EU/mL), LTA (4.53 [3.58-5.97] vs. 43.2 [23.2-109] pg/mL), and detection of bactDNA (≥ 5 pg/mL; 5% vs. 41%) were markedly higher in patients with ACLD than healthy controls (n = 40; p < 0.001) but were similar between different clinical stages of compensated and decompensated ACLD and displayed no meaningful correlation with HVPG and systemic hemodynamics. TNF-α and IL-10 correlated with LPS (Spearman's rs = 0.523, p < 0.001/rs = 0.143, p = 0.024) but not with LTA. Presence of bactDNA was associated with higher LPS (0.54 [0.28-0.95] vs. 0.88 [0.32-1.31] EU/mL, p = 0.001) and TNF-α (15.3 [6.31-28.1] vs. 20.9 [13.8-32.9] pg/mL). Patients with ACLD exhibited a decreased CD4:CD8-ratio and increased TH1-cells in the intestinal mucosa as compared to controls. During a median FU of 14.7 (8.20-26.5) months, bacterial antigens did not predict decompensation or liver-related death (in contrast to HVPG, IL-6, and MAP) as well as infections at 24 months. Conclusion: BT occurs already in early ACLD stages and triggers a systemic inflammatory response via TNF-α and IL-10. Interestingly, BT markers showed no clear correlation with portal hypertension and circulatory dysfunction in patients with stable ACLD.
publishDate 2023
dc.date.none.fl_str_mv 2023
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/11000/31334
url https://hdl.handle.net/11000/31334
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv https://doi.org/10.1007/s12072-023-10496-y
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
rights_invalid_str_mv Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.format.none.fl_str_mv application/pdf
12
application/pdf
dc.publisher.none.fl_str_mv Springer
publisher.none.fl_str_mv Springer
dc.source.none.fl_str_mv reponame:REDIUMH. Depósito Digital de la UMH
instname:Universidad Miguel Hernández de Elche
instname_str Universidad Miguel Hernández de Elche
reponame_str REDIUMH. Depósito Digital de la UMH
collection REDIUMH. Depósito Digital de la UMH
repository.name.fl_str_mv
repository.mail.fl_str_mv
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